Glucocorticolds in Fiber Repair and Regeneration of Dystrophic Muscles
ANF/MDA Co-Funded Grant
Mattia Quattrocelli, PhD
Center for Genetic Medicine, Northwestern University, Chicago, IL
Muscular dystrophies are characterized by chronic disruption of muscles, with consequent wasting of muscle. Normally, in response to muscle injury that disrupts the membrane around muscle, there is a repair complex that seals the damage. In dystrophic muscle, however, this process is impaired and in addition, dystrophic muscle do not regenerate as well as normal muscles. At present, glucorticoid steroids are the only pharmacological treatment for Duchenne Muscular Dystrophy. However, the side effects are prominent and the role of glucorticoids on the actual fiber repair process is still unknown. Moreover, the effects of glucorticoids on the stem cells in muscle are not well studied.
With this project, we aim to define the effects of glucorticoids on muscle membrane repair and regeneration in dystrophic muscles using newly developed methods. We will first test the effects of pulsed and chronic administration of glucorticoids on fiber repair and resident stem cells of dystrophic muscles. We will then examine how glucocorticoids counteract the negative effects of the TGFß molecular pathway on muscle repair and regeneration. Finally, we will study how glucocorticoids and the novel genetic modifier Jagged converge towards beneficial effects on dystrophic muscles.
- $180,000 paid over 3 years (co-funded with Muscular Dystrophy Association).
- $1,500 travel award to attend the AANEM Annual Meeting and present the research following completion of the project.
- Complimentary AANEM Annual Meeting registration in the year the research is presented.
- Complimentary AANEM membership for duration of funding period and a subscription to Muscle & Nerve during the duration of your project.
"This award will support me in critically advancing knowledge about the action of steroids in muscle on two parallel fronts."